Using Bacteria to Fight Cancer with Immunotherapies

Cancer researchers led by Weizmann Institute of Science have discovered that the immune system "sees" bacteria residing within tumor cells. These bacteria can be harnessed to provoke an immune reaction against the tumor.

"Our findings suggest that bacterial peptides presented on tumor cells can serve as potential targets for immunotherapy," says research leader Yardena Samuels. "They may be exploited to help immune T cells recognize the tumor with greater precision, so that these cells can mount a better attack against the cancer. This approach can in the future be used in combination with existing immunotherapy drugs."

A variety of species of bacteria are known to colonize human tumors, and modulate immune function. This ultimately affects the survival of patients with cancer and their responses to treatment.

A study is published in Nature. It reveals that peptides (fragments of proteins) derived from intracellular bacteria can be present in a tumor cell and provoke immune reactions. The study provides insight into a mechanism by which bacteria influence activation of the immune system and responses to therapy.

The researchers analyzed tissue samples from nine patients with metastatic melanoma, a deadly form of skin cancer. They obtained bacterial genomic profiles of these tumors and then identified tumor peptides that can be recognized by the immune system.

The study revealed nearly 300 peptides from 41 different bacteria on the surface of the cancer cells. The researchers found that the peptides were present in protein complexes that are present on the membranes of all cells in our body. These protein complexes "present" foreign peptides to the immune system so that immune cells can "see" them.

Some of the bacteria identified in the study were known gut microbes. This could shed light on how the gut microbiome - the bacteria, viruses, and fungi present in the gastrointestinal tract - affects immunotherapy.

The fact that bacterial peptides on tumor cells are visible to the immune system can be exploited for enhancing immunotherapy. "Many of these peptides were shared by different metastases from the same patient or by tumors from different patients, which suggests that they have a therapeutic potential and a potent ability to produce immune activation," says researcher Adi Nagler.

Future studies are planned to establish which bacterial strains help the immune cells to fight cancer. This could enable physicians to predict the success of immunotherapy and to tailor a personalized treatment accordingly.

Cancer immunotherapies have dramatically improved recovery rates from certain cancers, including metastatic melanoma. But cancer immunotherapies still work in only about 40 percent of melanoma patients.

These findings reveal an entirely new type of interaction between tumors and the immune system. And they could open the door to new, more effective forms of cancer immunotherapy.